From SNPedia
| Geno
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Mag
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Summary
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| (A;A)
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4
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Two copies of H36D, likely affected by hemochromatosis which may be serious if male or post-menopausal.
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| (A;G)
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3
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One copy of C282Y, carrier of hemochromatosis, likely unaffected unless also H63D carrier.
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| (G;G)
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0
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Not a C282Y hemochromatosis carrier.
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| ? | (A;A) (A;G) (G;G) | 28 |
 |
rs1800562 represents a SNP that accounts for ~85% of all cases of hemochromatosis, a disorder whose symptoms include cirrhosis of the liver, diabetes, hypermelanotic pigmentation of the skin, and heart failure. OMIM indicates that liver cancer is responsible for about one-third of deaths of rs1800562(A;A) homozygotes, and since hemochromatosis is a relatively easily treated disorder if diagnosed, this is a form of preventable cancer.
The rs1800562(A) allele is known as the C282Y mutation, and it is found at a frequency of around 5-10% in many Caucasian populations, leading to an incidence of (A;A) homozygotes around 1 in 200. Early identification of rs1800562(A;A) homozygotes can prevent complications of hemochromatosis; however, the percentage of all (A;A) homozygotes who actually develop clinical signs of hemochromatosis may be relatively low, may depend on sex (see below), and appears to be influenced by other SNPs yet to all be discovered as well as (unidentified) environmental factors, possibly including the amount of iron in the diet.
In rs1800562(A;A) patients who do develop hemochromatosis, a SNP has been identified which increases the risk of cardiomyopathy (a form of heart disease). rs4880(T;T) homozygotes are at ~10 fold increased risk for dilated- or non-dilated cardiopathy based on a study of 217 patients.[PMID 15591282]
rs235756, a SNP in the BMP2 gene, is another SNP that may influence the development of hemochromatosis in rs1800562(A;A) individuals, at least if serum transferrin levels are a good indication. Transferrin levels increased with increasing copies of the rs235756(T) allele.[PMID 17847004]
So which rs1800562(A;A) individuals actually develop clinical signs of hemochromatosis? In a recent study of ~200 rs1800562(A;A) homozygotes, ~30% of the males had iron-overload related diseases versus 1% of the females. Male C282Y homozygotes with a serum ferritin level of 1,000 mcg per liter or more were more likely to report fatigue, use of arthritis medicine, and a history of liver disease than were men who lacked a rs1800562(A) allele.[PMID 18199861]
Women who are rs1800562(A) homozygotes are less affected by hemochromatosis due to elimination of excess iron during menstruation, but may become affected after menopause.
Carriers of rs1800562(A) may be affected by a mild form of hemochromatosis if also a carrier of rs1799945(G) H63D.
According to Coriell, in Caucasian populations:
- (A;A) - 0.4% of individuals, carrying 2 copies of the risk variant (33-57% of such males will have quite elevated iron levels; 3-16% if female)
- (G;A) - 12% carry 1 copy of the risk variant and 1 copy of the non-risk variant
- (G;G) - 87.6% carry (only) the non-risk variant
| GWAS snp
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| PMID
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[PMID 19820697]
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| Trait
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Hematological parameters
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| Title
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A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
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| Risk Allele
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A
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| P-val
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1E-23
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| Odds Ratio
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1.41 [1.13-1.69] fl increase
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| GWAS snp
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| PMID
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[PMID 19862010]
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| Trait
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Hematocrit
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| Title
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Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium
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| Risk Allele
|
A
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| P-val
|
2E-9
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| Odds Ratio
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0.31 [0.21-0.41] % increase
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| PharmGKB | PA164920576 |
| Name | |
| Annotation | In a GWAS performed on 459 female monozygotic twin pairs, all Australians of European descent, this SNP was found to be associated with serum iron (p=3.5 x 10 (-11)), serum transferrin (p = 1.1 x 10 (-10)), transferrin saturation (p=4.3 x 10 (-15)) and serum ferritin (p=4.5 x 10(-5)). |
| Gene | HFE |
| Featue | |
| Evidence | PubMed ID:19084217 |
| Drugs | |
| Diseases | |
| Curation Level | Curated |
[PMID 20029940] Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease
[PMID 20858683] Common variants at ten genomic loci influence hemoglobin A1C levels via glycemic and non-glycemic pathways
| GWAS snp
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| PMID
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[PMID 20927387]
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| Trait
|
|
| Title
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A genome-wide association study of red blood cell traits using the electronic medical record
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| Risk Allele
|
A
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| P-val
|
3E-9
|
| Odds Ratio
|
0.49 [0.33-0.65] unit increase
|
| PharmGKB | PA162652703 |
| Name | HFE:C282Y, HFE: Cys282Tyr |
| Annotation | HFE variants, HFE: His63Asp and HFE: Cys282Tyr, reduce the amount of r-HuEPO and iron necessary to support erythropoiesis in hemodialysis patients. |
| Gene | HFE |
| Featue | |
| Evidence | PubMed ID:18025780 |
| Drugs | epoetin alfa |
| Diseases | |
| Curation Level | Curated |
| PharmGKB | PA164740110 |
| Name | |
| Annotation | GWAS results: Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels. (Initial Sample Size: 459 twin pairs; Replication Sample Size: NR); (Region: 6p22.1; Reported Gene(s): HFE; Risk Allele: rs1800562-?); (p-value= 0.0000000001).This variant is associated with Serum markers of iron status(serum transferrin). |
| Gene | HFE |
| Featue | |
| Evidence | PubMed ID:19084217; Web Resource:http://www.genome.gov/gwastudies/ |
| Drugs | |
| Diseases | |
| Curation Level | Non-Curated |
| PharmGKB | PA164740112 |
| Name | |
| Annotation | GWAS results: Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels. (Initial Sample Size: 459 twin pairs; Replication Sample Size: NR); (Region: 6p22.1; Reported Gene(s): HFE; Risk Allele: rs1800562-?); (p-value= 0.00000000004).This variant is associated with Serum markers of iron status(serum iron). |
| Gene | HFE |
| Featue | |
| Evidence | PubMed ID:19084217; Web Resource:http://www.genome.gov/gwastudies/ |
| Drugs | |
| Diseases | |
| Curation Level | Non-Curated |
| PharmGKB | PA164740104 |
| Name | |
| Annotation | GWAS results: Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels. (Initial Sample Size: 459 twin pairs; Replication Sample Size: NR); (Region: 6p22.1; Reported Gene(s): HFE; Risk Allele: rs1800562-?); (p-value= 0.000000000000004).This variant is associated with Serum markers of iron status(transferrin saturation). |
| Gene | HFE |
| Featue | |
| Evidence | PubMed ID:19084217; Web Resource:http://www.genome.gov/gwastudies/ |
| Drugs | |
| Diseases | |
| Curation Level | Non-Curated |
| GWAS snp
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| PMID
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[PMID 21665994]
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| Trait
|
|
| Title
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Genome-wide association study identifies two loci strongly affecting transferrin glycosylation.
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| Risk Allele
|
A
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| P-val
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2E-32
|
| Odds Ratio
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0.6290 [0.53-0.73] unit decrease
|
| GWAS snp
|
| PMID
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[PMID 21785125]
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| Trait
|
|
| Title
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Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations.
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| Risk Allele
|
|
| P-val
|
3E-7
|
| Odds Ratio
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0.3890 [0.24-0.54] ng/ml increase
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| GWAS snp
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| PMID
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[PMID 21943158]
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| Trait
|
|
| Title
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Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits.
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| Risk Allele
|
A
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| P-val
|
5E-12
|
| Odds Ratio
|
0.1770 [0.13-0.23] mg/l increase
|
| GWAS snp
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| PMID
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[PMID 20686565]
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| Trait
|
|
| Title
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Biological, clinical and population relevance of 95 loci for blood lipids.
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| Risk Allele
|
A
|
| P-val
|
6E-10
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| Odds Ratio
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2.2200 None
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